Baker, DavidChidyausiku, Tamuka Martin2019-05-022019-05-022019Chidyausiku_washington_0250O_19789.pdfhttp://hdl.handle.net/1773/43639Thesis (Master's)--University of Washington, 2019β-sheet proteins carry out critical functions in biology, and hence are attractive scaffolds for computational protein design. Through study of loops connecting unpaired β-strands (β-arches), we have identified a series of structural relationships between loop geometry, side chain directionality and β-strand length that arise from hydrogen bonding and packing constraints on regular β-sheet structures. We use these rules to de novo design jellyroll structures with double-stranded β-helices formed by eight antiparallel β-strands. The nuclear magnetic resonance structure of a hyperthermostable design closely matched the computational model, demonstrating accurate control over the β-sheet structure and loop geometry. Our results open the door to the design of a broad range of non-local β-sheet protein structures.application/pdfen-USCC BY-NC-SAbeta-sheetsDe novojellyrollrosettastableBiochemistryBioengineeringBiological chemistryThesis